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2-Acylimino-3-alkyl-3H-thiazolinederivatives:one-pot,three-componentcondensationsynthesisofnovelb-turnmimicsAkiraManaka,*TakaakiIshii,KeikoTakahashiandMasakazuSatoMedicinalChemistryLaboratory,MedicinalResearchLaboratories,TaishoPharmaceuticalCo.Ltd,403,1-chome,Yoshino-cho,Kita-ku,Saitama-shi,Saitama331-9530,JapanReceived20August2004;revised17November2004;accepted19November2004Abstract—One-pot,three-componentcondensationofaroylthiourea,primaryamineanda-halocarbonylderivativesforthesynthe-sisof2-acylimino-3-alkyl-3H-thiazolinederivativesisdescribed.Thismethodisusefulforsimultaneouslyincorporatingdiversefunctionalgroupsatfourpositionsinthe3H-thiazolineskeletontoobtainb-turntripeptidemimics.?2004ElsevierLtd.Allrightsreserved.Theb-turnstructureisformedbyintramolecularhydro-genbondinginatripeptidesubstructureattheproteinsurface,andiswellknowntoberecognizedasaligandbyvariousreceptors.1Numerousstudieshavebeenconductedonlow-molecular-weightcompounds,whichmimictheb-turnsubstructureofnaturalpolypeptideligandstoovercomethepharmacokineticdisadvantagesofpeptideligands.Severallow-molecular-weightmimicsoftheRGDsequenceon?brinogenhavebeenreported,andtheseexhibitstronginhibitoryactivitiesagainstthebindingof?brinogentoitsreceptorGPIIb/IIIa.2Wehavealsoreportedaunique3-alkyl-3H-thiazolinederiva-tivePS-028(1)asapotentandselectiveGPIIb/IIIaantagonist(Fig.1,Ki=46.5±5.8pM).3The3-alkyl-3H-thiazolineskeletonofPS-028canbefunctionalizedatfourpositions,andthereforehaspotentialasaversa-tiletemplateforotherb-turnmimics.Incourseofaninvestigationoffunctionalizationon3-alkyl-3H-thiazo-lineskeleton,wehavefoundthattheintroductionofasubstituentotherthanasmallalkylgroupatthe3-posi-tionoftheskeletonislimitedbythelowreactivitytowardalkylhalides(Scheme1).Asanalternativemethodtoprepare3-alkyl-3H-thiazolineskeleton,con-densationreactionofN-acyl-N0-alkylthioureaanda-halocarbonylderivativeisreported.4However,therea
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